A First-in-human, Phase I, Single-center, Open-label, Dose-escalation Trial in Healthy Volunteers to Assess Safety, Tolerability, and Immunogenicity of PANHPVAX, a Vaccine Targeting Human Papilloma L2 Antigen Formulated With Cyclic Di-AMP

First-in-human, phase I, single-center, open-label, dose-escalation trial in healthy volunteers. Investigation of safety and tolerability of ascending doses of PANHPVAX, a vaccine against human papilloma L2 antigens formulated with cdA (adjuvant) as compared to the formulation without cdA.

开始日期2022-11-01

申办/合作机构

German Cancer Research Center

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100 项与 Human Papillomavirus Vaccine(German Cancer Research Center) 相关的临床结果

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100 项与 Human Papillomavirus Vaccine(German Cancer Research Center) 相关的转化医学

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100 项与 Human Papillomavirus Vaccine(German Cancer Research Center) 相关的专利（医药）

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项与 Human Papillomavirus Vaccine(German Cancer Research Center) 相关的文献（医药）

npj Vaccines

Inter-epitope spacer variation within polytopic L2-based human papillomavirus antigens affects immunogenicity

Article

作者: Kreuziger, Tim ; Koenig, Karl Moritz ; Ottonello, Simone ; Sehr, Peter ; Çelikyürekli, Simay ; Spagnoli, Gloria ; Mariz, Filipe Colaco ; Zhang, Yueru ; Zhao, Xueer ; Bolchi, Angelo ; Müller, Martin

AbstractThe human papillomavirus minor capsid protein L2 is being extensively explored in pre-clinical studies as an attractive vaccine antigen capable of inducing broad-spectrum prophylactic antibody responses. Recently, we have developed two HPV vaccine antigens – PANHPVAX and CUT-PANHPVAX- both based on heptameric nanoparticle antigens displaying polytopes of the L2 major cross-neutralizing epitopes of eight mucosal and twelve cutaneous HPV types, respectively. Prompted by the variable neutralizing antibody responses against some of the HPV types targeted by the antigens observed in previous studies, here we investigated the influence on immunogenicity of six distinct glycine-proline spacers inserted upstream to a specific L2 epitope. We show that spacer variants differentially influence antigen immunogenicity in a mouse model, with the antigen constructs M8merV6 and C12merV6 displaying a superior ability in the induction of neutralizing antibodies as determined by pseudovirus-based neutralization assays (PBNAs). L2-peptide enzyme-linked immunosorbent assay (ELISA) assessments determined the total anti-L2 antibody level for each antigen variant, showing for the majority of sera a correlation with their repective neutralizing antibody level. Surface Plasmon Resonance revealed that L2 epitope-specific, neutralizing monoclonal antibodies (mAbs) display distinct avidities to different antigen spacer variants. Furthermore, mAb affinity toward individual spacer variants was well correlated with their neutralizing antibody induction capacity, indicating that the mAb affinity assay predicts L2-based antigen immunogenicity. These observations provide insights on the development and optimization of L2-based HPV vaccines.

Frontiers in Immunology

Next generation L2-based HPV vaccines cross-protect against cutaneous papillomavirus infection and tumor development

Article

作者: Ahmels, Melinda ; Braspenning-Wesch, Ilona ; Mariz, Filipe C ; Hasche, Daniel ; Kirnbauer, Reinhard ; Rösl, Frank ; Huber, Bettina ; Stephan, Sonja ; Cao, Rui ; Müller, Martin ; Schmidt, Gabriele

Licensed L1-VLP-based immunizations against high-risk mucosal human papillomavirus (HPV) types have been a great success in reducing anogenital cancers, although they are limited in their cross-protection against HPV types not covered by the vaccine. Further, their utility in protection against cutaneous HPV types, of which some contribute to non-melanoma skin cancer (NMSC) development, is rather low. Next generation vaccines achieve broadly cross-protective immunity against highly conserved sequences of L2. In this exploratory study, we tested two novel HPV vaccine candidates, HPV16 RG1-VLP and CUT-PANHPVAX, in the preclinical natural infection model Mastomys coucha. After immunization with either vaccines, a mock control or MnPV L1-VLPs, the animals were experimentally infected and monitored. Besides vaccine-specific seroconversion against HPV L2 peptides, the animals also developed cross-reactive antibodies against the cutaneous Mastomys natalensis papillomavirus (MnPV) L2, which were cross-neutralizing MnPV pseudovirions in vitro. Further, both L2-based vaccines also conferred in vivo protection as the viral loads in plucked hair after experimental infection were lower compared to mock-vaccinated control animals. Importantly, the formation of neutralizing antibodies, whether directed against L1-VLPs or L2, was able to prevent skin tumor formation and even microscopical signs of MnPV infection in the skin. For the first time, our study shows the proof-of-principle of next generation L2-based vaccines even across different PV genera in an infection animal model with its genuine PV. It provides fundamental insights into the humoral immunity elicited by L2-based vaccines against PV-induced skin tumors, with important implications to the design of next generation HPV vaccines.

100 项与 Human Papillomavirus Vaccine(German Cancer Research Center) 相关的药物交易

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